Endotoxemia is defined as the presence of an elevated level of lipopolysaccharides (also known as endotoxins) in the body. Lipopolysaccharides (LPS), also known as lipoglycans, are large molecules consisting of at least one lipid moiety and at least one polysaccharide moiety joined by a covalent bond. LPS are found in the outer membrane of Gram-negative bacteria, act as endotoxins and elicit strong immune responses in animals.
Cani et al., Diabetes, 2007, 56, 1761-1772, describes the induction of an increase in endotoxemia in mice fed a high-fat diet. The authors found that plasma LPS concentration varies throughout the day, increasing to a maximum at the end of the dark, feeding period for mice fed a normal diet, and that a high-fat diet caused endotoxemia to be high throughout the day. The authors define the term ‘metabolic endotoxemia’ as a chronic, 2- to 3-fold increase in plasma lipopolysaccharides (LPS) concentration from baseline levels, induced by a high-fat diet, and note that the endotoxemia levels reached was 10-50 times lower than that obtained during septic shock.
Bacterial translocation is defined as the passage of viable bacteria from the intestinal tract through the epithelial mucosa into the body. Bacteria may enter the lymphatic system via mesenteric lymph nodes and therefore may be circulated systemically. Bacteria can also enter blood circulation (bacteremia) and may also be located in tissues. Bacterial translocation may occur in a number of medical conditions, including intestinal bacterial overgrowth, intestinal injury and shock. Any medical condition associated with increased intestinal permeability can potentially lead to bacterial translocation.
As LPS originate from bacteria in the gut, translocation of bacteria from the gut into the body may potentially serve as a potential mechanism for endotoxemia, including metabolic endotoxemia. If Gram-negative bacteria translocate into the body, they serve as a source of LPS. However, the exact route of LPS into the body in metabolic endotoxemia is currently unknown: bacterial translocation is considered one possible explanation, but free LPS from the gut may also enter the body during normal lipid absorption. It is also possible that several mechanisms take place at the same time.
Schiffrin et al., Br. J. Nutr., 2009, 101, 961-966, describe the use of a probiotic yogurt supplement in elderly patients with small-intestinal bacterial overgrowth (SIBO). The effects on intestinal colonisation, gut permeability, endotoxin translocation and modification of innate immune functions were assessed. However, the endotoxemia in the patients described in this document is septic shock endotoxemia, which is caused by infection with pathogens, such as pathogenic bacteria, and in which, as described in the Cani et al. article referred to above, plasma LPS levels are increased by a much larger factor from normal levels. This is distinct from metabolic endotoxemia, which as described above is generally caused by diet (in particular, by a high-fat diet) and in which the increase in plasma LPS levels (expressed as a multiple of normal levels) is much lower.